title: Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids.
abstract: OBJECTIVE
  To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience.
  
  
  METHODS
  We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates.
  
  
  RESULTS
  Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis.
  
  
  CONCLUSIONS
  ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.
authors.affiliation: Thoracic Surgery Unit, Perugia University School of Medicine, Perugia, Italy.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Daddi
authors.forename: Marco
authors.initials: M
authors.lastname: Schiavon
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Filosso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cardillo
authors.forename: Marcello Carlo
authors.initials: MC
authors.lastname: Ambrogi
authors.forename: Angela
authors.initials: A
authors.lastname: De Palma
authors.forename: Luca
authors.initials: L
authors.lastname: Luzzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bandiera
authors.forename: Christian
authors.initials: C
authors.lastname: Casali
authors.forename: Alberto
authors.initials: A
authors.lastname: Ruffato
authors.forename: Verena
authors.initials: V
authors.lastname: De Angelis
authors.forename: Luigi Gaetano
authors.initials: LG
authors.lastname: Andriolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Guerrera
authors.forename: Francesco
authors.initials: F
authors.lastname: Carleo
authors.forename: Federico
authors.initials: F
authors.lastname: Davini
authors.forename: Moira
authors.initials: M
authors.lastname: Urbani
authors.forename: Sandro
authors.initials: S
authors.lastname: Mattioli
authors.forename: Uliano
authors.initials: U
authors.lastname: Morandi
authors.forename: Piero
authors.initials: P
authors.lastname: Zannini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gotti
authors.forename: Michele
authors.initials: M
authors.lastname: Loizzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Puma
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Alberto
authors.initials: A
authors.lastname: Ricci
authors.forename: Alberto
authors.initials: A
authors.lastname: Oliaro
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery* / Q000628:therapy; D008197:Lymph Node Excision / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013510:Pulmonary Surgical Procedures / Q000379:methods; D012189:Retrospective Studies; D055815:Young Adult
keywords: Adjuvant therapy; Atypical carcinoids; Chemotherapy; Multicentric forms; Surgery; Tumourlets